Fainting (i.e. orthostatic intolerance), or symptoms associated with fainting account for 3% of all emergency room visits and 6% of all hospital admissions. A combination of the heat stress with orthostasis leads to pronounced and consistent reductions in orthostatic tolerance during upright tilt, gravitational acceleration, and lower-body negative pressure. Despite clear evidence of marked reductions in orthostatic tolerance in hyperthermic individuals, the mechanisms responsible for the reduction in orthostatic tolerance in heat stressed individuals is incompletely understood. It has been suggested that increased muscle temperature may attenuate alpha-adrenergic vasoconstriction; however, the effect of heat on baroreflex-mediated vasoconstriction and specifically the alpha-adrenergic responsiveness in human limbs is incompletely understood. Although redistribution of cardiac output to the skin is likely to contribute in part to the reduction in orthostatic tolerance with whole-body heating, it remains unknown as to whether autonomic control (i.e. the baroreflex) of the vasculature supplying other organs such as skeletal muscle is reduced, further challenging the maintenance of arterial blood pressure during heat stress. Therefore, the goal of the projects outlined in this proposal is to test the hypothesis that increased temperature attenuates baroreflex-mediated vasoconstriction and that this event occurs through reduced alpha-adrenergic receptor responsiveness in human limbs. [unreadable] [unreadable] [unreadable]